Superoxide Dismutase: Free Radical Degradation in Health and Disease

Abstract

Oxygen is necessary for sustaining human life; however, toxic and reactive superoxide free radicals spontaneously form during cellular metabolism. These free radicals are highly reactive and harmful to the body if not degraded by superoxide dismutase (SOD). The eukaryotic, cytoplasmic isoform, CuZn SOD, converts toxic superoxide into hydrogen peroxide or oxygen. Subsequently, the enzymes catalase and glutathione peroxidase aid the conversion of hydrogen peroxide into oxygen and water. The CAPS (Center for Advanced Professional Studies) SMART (Students Modeling A Research Topic) Team modeled CuZn SOD using 3D printing technology to understand its molecular structure and function. CuZn SOD is a homodimer with each subunit composed of an eight flattened beta‐barrel fold. The funnel‐shaped active site containing copper and zinc cations attract negatively charged superoxide radicals. Cu is coordinated by His46, His48, His63, and His120, while Zn is coordinated by His63, His71, His80, and Asp83. The dismutation reaction begins when Cu2+ removes an electron from one superoxide. Then, as Cu+ it donates this added electron to a second superoxide, which is rapidly neutralized by two hydrogen ions, forming hydrogen peroxide. Mutations in the SOD1 gene greatly decrease enzyme activity. 15‐20% of familial amyotrophic lateral sclerosis (ALS) cases are caused by such mutations. Excess SOD is also harmful: in Down's Syndrome, trisomy of the SOD1 locus on chr 21 leads to increased CuZn SOD levels which indirectly contribute to the neurological symptoms of this disease. It is anticipated that future study of CuZn SOD may bring relief to patients with these debilitating conditions.